Is gynaecomastia a common side effect of antipsychotic medications?

Gynecomastia as a Side Effect of Antipsychotics

Yes, gynecomastia is a recognized side effect of antipsychotic medications, primarily associated with those that cause hyperprolactinemia, though it is relatively uncommon compared to other side effects. 1

Mechanism and Prevalence

Gynecomastia from antipsychotics occurs primarily through:

1. Hyperprolactinemia: Many antipsychotics block dopamine D2 receptors in the tuberoinfundibular pathway, removing the tonic inhibition of prolactin secretion 2

   • Elevated prolactin can lead to breast tissue growth in males
   • Prolactin levels can rise 10-fold or more above pretreatment values during antipsychotic treatment

2. Hormonal imbalance: Disruption of the estrogen-to-testosterone ratio, which is a key factor in gynecomastia development 1

Antipsychotic-Specific Risk

Antipsychotics can be categorized as "prolactin-raising" or "prolactin-sparing" based on their likelihood to cause hyperprolactinemia 2:

Higher Risk (Prolactin-raising):

• First-generation (typical) antipsychotics: Higher overall risk 2
• Risperidone: Significantly higher risk compared to other atypical antipsychotics 3
  • Studies show risperidone has 4.32 times higher odds of causing gynecomastia compared to quetiapine (OR = 4.32,95% CI: 1.31 to 14.27) 3
• Paliperidone: Similar risk profile to risperidone 4
• Amisulpride: Associated with significant hyperprolactinemia 2

Lower Risk (Prolactin-sparing):

• Aripiprazole: Rare occurrence of gynecomastia (listed as "rare" in FDA labeling) 5
• Clozapine: Low risk of hyperprolactinemia and gynecomastia 2
• Quetiapine: Lower risk; often used as an alternative when gynecomastia occurs with other agents 6
• Olanzapine: Lower risk than typical antipsychotics but higher than clozapine or quetiapine 2
• Ziprasidone: Rarely causes significant hyperprolactinemia 2

Clinical Considerations

Monitoring and Detection

• Regular physical examination to detect early breast tissue changes 1
• Consider baseline hormone levels in high-risk patients 1
• Be aware that patients may not report symptoms due to embarrassment

Associated Symptoms

Patients with antipsychotic-induced gynecomastia may also experience:

• Sexual dysfunction (reported in approximately 45% of patients on conventional antipsychotics) 2
• Galactorrhea (reported in approximately 19% of patients) 2
• Decreased libido and arousal 6

Management Options

When gynecomastia occurs:

1. Medication adjustment:

   • Switch to a prolactin-sparing antipsychotic (aripiprazole, clozapine, quetiapine) 6
   • Consider dose reduction if clinically feasible 2

2. Pharmacological interventions:

   • Addition of aripiprazole to the current regimen may help reduce prolactin levels 7
   • Dopamine agonists (cabergoline, bromocriptine) can be considered but may compromise antipsychotic efficacy 4

3. Surgical options:

   • For long-standing gynecomastia (>12-24 months) that doesn't respond to medication changes 1
   • Liposuction, direct excision, or combined approaches may be considered 1

Clinical Pitfalls to Avoid

1. Underestimation: Clinicians often underestimate the prevalence of prolactin-related side effects 2

2. Misdiagnosis: Ensure proper differentiation between true gynecomastia (glandular tissue) and pseudogynecomastia (fatty tissue deposition) 1

3. Incomplete evaluation: When gynecomastia occurs, don't automatically assume it's medication-related without ruling out other causes:

   • Tumors in the hypothalamic-pituitary area
   • Other medications
   • Underlying endocrine disorders

4. Long-term consequences: Be aware of potential long-term effects of untreated hyperprolactinemia:

   • Bone mineral density loss in both men and women 2
   • Potential increased risk of breast cancer (though data are conflicting) 2

By understanding the risk profiles of different antipsychotics and implementing appropriate monitoring and management strategies, clinicians can effectively address gynecomastia when it occurs as a side effect of antipsychotic treatment.